Is there an immunologic basis for schizophrenia?

The cause of schizophrenia remains an enigma despite the development of effective antipsychotic drugs that act by modulating the dopaminergic and serotonergic systems in the limbic region of the brain. Although such drugs are undoubtedly clinically effective, many patients do not fully benefit from such treatments, and the side effects, such as weight gain and the exacerbation of insulin-dependent diabetes mellitus, are often problematic. In recent years, the possible cause of schizophrenia has switched from an emphasis on neurotransmitter dysfunction to possible genetic and neurodevelopmental abnormalities. The close link between the loci for insulin-dependent diabetes mellitus, human lymphocyte antigen system and schizophrenia may indicate an immune component for this disorder. This hypothesis gains further credibility from epidemiologic studies showing a link between viral infections in utero and the subsequent development of schizophrenia; the negative correlation between rheumatoid arthritis and schizophrenia gives further support to the hypothesis. Thus, the immune hypothesis of schizophrenia has developed from an understanding of the genetic, environmental and infectious sequelae that underlie the immune changes involving the cellular and humoral components of the adaptive immune system. The changes in the types of T-lymphocytes that are involved in the adaptive immune response are of particular importance. The T-helper 1 cells, that secrete interleukin-2 and interferon-gamma for example, are reduced in activity while the T-helper 2 cells, together with the macrophages, show an increased secretion of interleukins-6 and -10. As these immune changes are normalized following effective antipsychotic drug treatment, new types of antipsychotics could be developed that act directly on the imbalance in the components of the adaptive immune system. The finding that some anti-inflammatory drugs can exhibit modest antipsychotic activity is further evidence of the validity of the autoimmune nature of schizophrenia and an indication that drug development based on this concept may be a fruitful area for future research.